%0 Journal Article
%A Ortín, Irene
%A Ochoa-Callejero, Laura
%A Werner, Christian
%A Lindenblatt, Dirk
%A Niefind, Karsten
%A Martínez, Alfredo
%A de Pascual-Teresa, Beatriz
%A Ramos, Ana Sofia
%T Targeting Casein Kinase 2 and Histone Deacetylase with a Dual Inhibitor Effectively Reduces Tumor Growth in a Triple-Negative Breast Cancer Xenograft Model
%J ACS pharmacology & translational science
%V 8
%N 7
%@ 2575-9108
%C Washington, DC
%I ACS Publications
%M PUBDB-2025-04033
%P 2093 - 2105
%D 2025
%Z Deutsche Forschungsgemeinschaft (DFG), grants NI 643/4-1 and NI 643/11-1.  Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Grant No. INST 216/682-1 FUGG. 
%X In a previous study, IOR-160 was identified as a potent dual inhibitor of CK2 and HDAC enzymes. In this study, we evaluated its selectivity and therapeutic potential. IOR-160 exhibited high selectivity for CK2 within a panel of 21 kinases and more widespread inhibitory activity against histone deacetylases (HDAC 1, 2, 3, and 6, low activity for HDAC8). Using a mouse model of triple-negative breast cancer (MDA-MB-231), we further explored its effects on disease progression. Notably, animals treated with IOR-160 exhibited no detectable signs of toxicity or behavioral side effects relative to untreated mice. In a xenograft study, IOR-160 significantly reduced tumor growth (p = 0.0336) and decreased tumor burden (p = 0.0454) compared to the vehicle (DMSO)-treated group. In addition, IOR-160 modulated critical cellular signaling pathways, demonstrated by the inhibition of AKT phosphorylation (p = 0.0175) and a significant increase in acetylated α-tubulin (p = 0.0023), confirming the dual action of IOR-160in vivo. Furthermore, X-ray crystallography revealed the binding mode of IOR-160 to CK2, showing high conservation compared to that of the known CK2 inhibitor CX-4945. These results suggest that IOR-160 has significant potential as an antitumor agent. Nonclinical and clinical studies become now necessary to validate the efficacy of this new chemical entity as a potential drug.
%F PUB:(DE-HGF)16
%9 Journal Article
%R 10.1021/acsptsci.5c00192
%U https://bib-pubdb1.desy.de/record/638315